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Expression and cellular provenance of thymic stromal lymphopoietin and chemokines in patients with severe asthma and chronic obstructive pulmonary disease
Comparison of Quality of Life of Asthmatic: Aspirin-Intolerant Asthma vs Atopic Asthma S. A. Zenokhov1, I. V. Sidorenko2, V. K. Treskunov1, T. V. Zakharzhevskaya2; 1Clinical Immunology, Scientific research institute of physical and chemical medicine, Moscow, RUSSIAN FEDERATION, 2Clinical Immunology and Allergology, Moscow Medical Academy of I.M. Setchenov, Moscow, RUSSIAN FEDERATION. RATIONALE: Patients with aspirin - intolerant asthma (AIA) and rhinitis have more limited social life than patients with atopic asthma and allergic rhinitis. METHODS: 68 adults with moderate to severe asthma aged 19-72 yrs were interviewed by using a validated Russian version Asthma Quality of Life Questionnaire(S)(AQLQ(S)), Rhinitis Symptoms Questionnaire(RSQ) and SF-36. Study population was divided into two groups. Patients with AIA have been included in the first group (N=39, FEV1=77.5±12.3% of predicted). Patients in the second group (N=29, FEV1=76.3±12.6% of predicted) had atopic persistent asthma with house dust mite sensitization. The AQLQ(S) has 32 items in four domains: activity limitation, symptoms, emotional functions and environmental stimuli. The response option for each item is on a 7 point scale where 1 indicates the maximum impairment and 7 indicates the absence of impairment. The RSQ includes five item with 5-point scales (up 0=absent to 4= very severe).The SF-36 includes multi-item scales that assess eight health concepts. RESULTSof study showed an insignificant difference (3.7/7vs 4.0/7) in the quality of life (QOL) scores for patients with AIA and atopic asthmatics assessed by AQLQ(S). However rhinitis symptoms were found to be on a higher scale in patients with AIA (average 8.88) than in atopic asthmatics (average5.04), p <0.005.AIA patients had more significantly lower general health perceptions, physical and social functioning as compared with atopic asthmatics.AIA patients had very important problems at work or in other daily activities associated with rhinitis symptoms. CONCLUSIONS: Patients with AIA have a lower QOL than patients with atopic asthma due to more severe rhinitis.
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Anti-Inflammatory Effects of Modern Histamine H1-Receptor Antagonists in Atopic Asthma D. K. C. Lee1, K. C. Khoo2, B. J. Lipworth3; 1Department of Respiratory Medicine, Ipswich Hospital, Heath Road, Ipswich IP4 5PD, England, UNITED KINGDOM, 2Department of Respiratory Medicine, Llandough Hospital, Penlan Road, Penarth CF64 2XX, Wales, UNITED KINGDOM, 3Asthma and Allergy Research Group, Ninewells Hospital and Medical School, University of Dundee, Dundee DD1 9SY, Scotland, UNITED KINGDOM. RATIONALE: Controversy exists as to the role of modern histamine H1receptor antagonists in the treatment of atopic asthma. METHODS: Forty-nine patients with atopic asthma were evaluated from three randomised double-blind placebo-controlled cross-over studies assessing the anti-inflammatory effects of desloratadine, fexofenadine, and levocetirizine at clinically recommended doses. RESULTS: Desloratadine, fexofenadine, and levocetirizine significantly improved (p < 0.05) the provocative concentration of adenosine monophosphate producing a 20% fall in forced expiratory volume in one second by 142% compared to placebo. There was a significant improvement (p < 0.05) of 15% in forced expiratory flow at 25% to 75% of maximal lung volume compared to placebo with desloratadine, fexofenadine, and levocetirizine. Fexofenadine significantly improved (p < 0.05) exhaled nitric oxide, domiciliary peak expiratory flow, and albuterol rescue use by 27%, 4%, and 83% respectively compared to placebo. There were no significant differences in all outcomes among the modern histamine H1-receptor antagonists. CONCLUSIONS: Modern histamine H 1 -receptor antagonists improve airway hyperresponsiveness, small-airways caliber, surrogate inflammatory markers, and asthma diary outcomes in patients with atopic asthma. Further studies are required to evaluate the effects of modern histamine H1-receptor antagonists on asthma exacerbations.
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Expression and Cellular Provenance of Thymic Stromal Lymphopoietin and Chemokines in Patients With Severe Asthma and Chronic Obstructive Pulmonary Disease S. Ying1, B. O’Connor1, J. Ratoff1, Q. Meng1, K. Mallett1, D. Cousins1, D. Robinson2, G. Zhang3, J. Zhao4, T. H. Lee1, C. Corrigan1; 1Asthma, Allergy & Respiratory Science, GKS Medical School, London, UNITED KINGDOM, 2Allergy and Leukocyte Biology Section, Imperial College School of Medicine, London, UNITED KINGDOM, 3Central Research, Third Clinical College, Jilin University, Changchun, CHINA, 4Central Research, Third Clincal College, Jilin University, Chang chun, CHINA. RATIONALE: Asthma and chronic obstructive pulmonary disease (COPD) are suggested to result from Th2-type and Th1-type airway inflammation respectively. Thymic stromal lymphopoietin (TSLP) favours Th2 type inflammation. We hypothesised that airways expression of TSLP and Th2-attracting chemokines is increased in asthma, but not COPD, where Th1-attracting chemokines predominate. METHODS: We used in situ hybridization and immunohistochemistry to examine the expression and cellular provenance of TSLP, Th2-attracting (TARC/CCL17, MDC/CCL22, and I-309/CCL1) and Th1-attracting (IP10/CXCL10 and TAC/CXCL11) chemokines in bronchial biopsies from 12 patients with severe asthma, 8 with COPD and 10 normal controls. RESULTS: The numbers of cells within the bronchial epithelium expressing mRNA for TSLP, TARC/CCL17, MDC/CCL22 and IP10/CXCL10, but not I-TAC/CXCL11 and I-309/CCL1, were significantly and equivalently increased in severe asthma and COPD as compared with controls. In the mucosa, the numbers of cells expressing these same molecules were significantly elevated in asthma as compared with controls, and intermediate in COPD, although not significantly elevated. TSLP and TARC/CCL17 expression correlated inversely with airways obstruction. Sequential IHC/ISH showed that epithelial cells, endothelial cells, neutrophils, macrophages and mast cells were the sources of TSLP and Th1 and Th2 attracting chemokines. The cellular provenance of these mediators was strikingly similar in severe asthma and COPD. CONCLUSIONS: Our data implicate TSLP and both Th1- and Th2attracting chemokines in the pathogenesis of asthma and COPD, and provide evidence for uniformity in the origins and expression of these mediators, particularly in the epithelium, in obstructive airways disease.
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Bronchus Suis Masquerading as Asthma
M. Reddy, R. Faust, E. A. Secord, M. Pansare; Wayne State University/Children’s Hospital of Michigan, Detroit, MI. RATIONALE: Multiple pathologic entities masquerade as asthma. We present a congenital anomaly that may mimic asthma in its presentation and if unidentified, may lead to respiratory complication. METHODS: A 9-month-old male was admitted for his third asthma exacerbation. After the first hospitalization day, he was noted to have persistent wheezing despite nebulized albuterol and a steroid burst, and inspiratory stridor. A chest X-ray demonstrated right lower lobe opacity, but no radio opaque foreign body. Bilateral decubitus films demonstrated equal lung volumes bilaterally. Direct laryngobronchoscopy was performed to evaluate for possible airway obstruction. RESULTS: A bronchus suis, or tracheal bronchus, was visualized. Tracheal bronchus is an anomaly in which the right upper lobe and its bronchus originate in the trachea, rather than distal to the carina. This is the normal configuration in swine, and hence the name “bronchus suis”, meaning “pig bronchus”. The incidence is from 0.001% to 2%. Affected individuals may be asymptomatic, or may have airway obstruction or recurrent pneumonia. Complications include obstruction of the tracheal bronchus with endotracheal intubations resulting in lobar collapse, pneumothorax or inadequate mechanical ventilation. Diagnosis is made by direct laryngobronchoscopy. Treatment is based on severity of symptoms, but is usually symptomatic. If pneumonia recurs, resection of the anomalous lobe and bronchus is the treatment of choice. CONCLUSIONS: Radiographic films are poorly sensitive in indicating airway obstruction. A strong index of suspicion should prompt further investigation of the airway with laryngobronchoscopy. This case reminds us “All that wheezes is not asthma”.
SATURDAY
Abstracts S9
J ALLERGY CLIN IMMUNOL VOLUME 115, NUMBER 2
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Anti-Inflammatory Effects of Modern Histamine H1-Receptor Antagonists in Atopic Asthma D. K. C. Lee1, K. C. Khoo2, B. J. Lipworth3; 1Department of Respiratory Medicine, Ipswich Hospital, Heath Road, Ipswich IP4 5PD, England, UNITED KINGDOM, 2Department of Respiratory Medicine, Llandough Hospital, Penlan Road, Penarth CF64 2XX, Wales, UNITED KINGDOM, 3Asthma and Allergy Research Group, Ninewells Hospital and Medical School, University of Dundee, Dundee DD1 9SY, Scotland, UNITED KINGDOM. RATIONALE: Controversy exists as to the role of modern histamine H1receptor antagonists in the treatment of atopic asthma. METHODS: Forty-nine patients with atopic asthma were evaluated from three randomised double-blind placebo-controlled cross-over studies assessing the anti-inflammatory effects of desloratadine, fexofenadine, and levocetirizine at clinically recommended doses. RESULTS: Desloratadine, fexofenadine, and levocetirizine significantly improved (p < 0.05) the provocative concentration of adenosine monophosphate producing a 20% fall in forced expiratory volume in one second by 142% compared to placebo. There was a significant improvement (p < 0.05) of 15% in forced expiratory flow at 25% to 75% of maximal lung volume compared to placebo with desloratadine, fexofenadine, and levocetirizine. Fexofenadine significantly improved (p < 0.05) exhaled nitric oxide, domiciliary peak expiratory flow, and albuterol rescue use by 27%, 4%, and 83% respectively compared to placebo. There were no significant differences in all outcomes among the modern histamine H1-receptor antagonists. CONCLUSIONS: Modern histamine H 1 -receptor antagonists improve airway hyperresponsiveness, small-airways caliber, surrogate inflammatory markers, and asthma diary outcomes in patients with atopic asthma. Further studies are required to evaluate the effects of modern histamine H1-receptor antagonists on asthma exacerbations.
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Expression and Cellular Provenance of Thymic Stromal Lymphopoietin and Chemokines in Patients With Severe Asthma and Chronic Obstructive Pulmonary Disease S. Ying1, B. O’Connor1, J. Ratoff1, Q. Meng1, K. Mallett1, D. Cousins1, D. Robinson2, G. Zhang3, J. Zhao4, T. H. Lee1, C. Corrigan1; 1Asthma, Allergy & Respiratory Science, GKS Medical School, London, UNITED KINGDOM, 2Allergy and Leukocyte Biology Section, Imperial College School of Medicine, London, UNITED KINGDOM, 3Central Research, Third Clinical College, Jilin University, Changchun, CHINA, 4Central Research, Third Clincal College, Jilin University, Chang chun, CHINA. RATIONALE: Asthma and chronic obstructive pulmonary disease (COPD) are suggested to result from Th2-type and Th1-type airway inflammation respectively. Thymic stromal lymphopoietin (TSLP) favours Th2 type inflammation. We hypothesised that airways expression of TSLP and Th2-attracting chemokines is increased in asthma, but not COPD, where Th1-attracting chemokines predominate. METHODS: We used in situ hybridization and immunohistochemistry to examine the expression and cellular provenance of TSLP, Th2-attracting (TARC/CCL17, MDC/CCL22, and I-309/CCL1) and Th1-attracting (IP10/CXCL10 and TAC/CXCL11) chemokines in bronchial biopsies from 12 patients with severe asthma, 8 with COPD and 10 normal controls. RESULTS: The numbers of cells within the bronchial epithelium expressing mRNA for TSLP, TARC/CCL17, MDC/CCL22 and IP10/CXCL10, but not I-TAC/CXCL11 and I-309/CCL1, were significantly and equivalently increased in severe asthma and COPD as compared with controls. In the mucosa, the numbers of cells expressing these same molecules were significantly elevated in asthma as compared with controls, and intermediate in COPD, although not significantly elevated. TSLP and TARC/CCL17 expression correlated inversely with airways obstruction. Sequential IHC/ISH showed that epithelial cells, endothelial cells, neutrophils, macrophages and mast cells were the sources of TSLP and Th1 and Th2 attracting chemokines. The cellular provenance of these mediators was strikingly similar in severe asthma and COPD. CONCLUSIONS: Our data implicate TSLP and both Th1- and Th2attracting chemokines in the pathogenesis of asthma and COPD, and provide evidence for uniformity in the origins and expression of these mediators, particularly in the epithelium, in obstructive airways disease.
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35
Bronchus Suis Masquerading as Asthma
M. Reddy, R. Faust, E. A. Secord, M. Pansare; Wayne State University/Children’s Hospital of Michigan, Detroit, MI. RATIONALE: Multiple pathologic entities masquerade as asthma. We present a congenital anomaly that may mimic asthma in its presentation and if unidentified, may lead to respiratory complication. METHODS: A 9-month-old male was admitted for his third asthma exacerbation. After the first hospitalization day, he was noted to have persistent wheezing despite nebulized albuterol and a steroid burst, and inspiratory stridor. A chest X-ray demonstrated right lower lobe opacity, but no radio opaque foreign body. Bilateral decubitus films demonstrated equal lung volumes bilaterally. Direct laryngobronchoscopy was performed to evaluate for possible airway obstruction. RESULTS: A bronchus suis, or tracheal bronchus, was visualized. Tracheal bronchus is an anomaly in which the right upper lobe and its bronchus originate in the trachea, rather than distal to the carina. This is the normal configuration in swine, and hence the name “bronchus suis”, meaning “pig bronchus”. The incidence is from 0.001% to 2%. Affected individuals may be asymptomatic, or may have airway obstruction or recurrent pneumonia. Complications include obstruction of the tracheal bronchus with endotracheal intubations resulting in lobar collapse, pneumothorax or inadequate mechanical ventilation. Diagnosis is made by direct laryngobronchoscopy. Treatment is based on severity of symptoms, but is usually symptomatic. If pneumonia recurs, resection of the anomalous lobe and bronchus is the treatment of choice. CONCLUSIONS: Radiographic films are poorly sensitive in indicating airway obstruction. A strong index of suspicion should prompt further investigation of the airway with laryngobronchoscopy. This case reminds us “All that wheezes is not asthma”.
SATURDAY
Abstracts S9
J ALLERGY CLIN IMMUNOL VOLUME 115, NUMBER 2